With the development of genetic engineering technology, various protein formulations became supplied in stable amounts. To ensure stability, these formulations are supplied in the dosage form of a lyophilized protein ingredient powder to be dissolved just before use in a separately packaged water-soluble diluent or in the dosage form of a protein solution formulation containing additives for improving stability.
Recently, efforts have been made to provide various antibody preparations in the form of solution formulations, but antibodies such as immunoglobulins, monoclonal antibodies and humanized antibodies are unstable proteins liable to physical or chemical changes such as association or aggregation under stresses of filtration, concentration and heating for removing viruses during the purification step. Antibody preparations also have the disadvantage that the biological activity of the antibodies decreases after long-term storage though it is essential for them to maintain the binding activity for their antigens in vivo.
A stabilization effect was found by adding polymers including proteins such as human serum albumin or purified gelatin or oligomers such as polyols, amino acids and surfactants as stabilizers for controlling chemical or physical changes. However, the addition of proteins such as human serum albumin or purified gelatin as stabilizers involves a very complicated step for removing viral contamination or other problems.
Acetyltryptophan was added to proteins such as albumin, human growth hormones and human B cell differentiation factor (BCDF) (JPB No. HEI7-68137, JPA No. HEI10-265404, JPA No. HEI3-27320). We previously reported stabilizing hematopoietic growth factors such as G-CSF and EPO by adding acetyltryptophan (PCT/JP01/01524).
However, it has not been so far known to stabilize antibody preparations by adding acetyltryptophan. Moreover, all the conventional preparations stabilized with acetyltryptophan described above were reported to show improved protein residuals by adding acetyltryptophan, but its effect on controlling the decrease in the biological activity in protein preparations, especially antibody preparations has not been known.